Using epidemiological data to guide clinical practice: review of studies on cardiovascular disease and use of combined oral contraceptives

Objective: To explore the usefulness of epidemiological data to guide clinical practice by seeking an answer to the question “What is the risk of cardiovascular disease among users of currently available, low dose, combined oral contraceptives who are aged less than 35 years, do not smoke, and do not have a medical condition known to increase the risk of vascular disease?”

Use of novel biomarkers (Homocysteine, vitamin B6, B9 and B12) on the assessing the progression of cardiovascular disease

A large number of evidences correlate elevated levels of homocysteine (Hcys) with a higher cardiovascular diseases (CVDs) risk, especially, atherosclerosis. Similarly, abnormal low levels of the vitamins B6, B9 and B12 are associated to an instability in the methionine cycle with an over production of Hcys. Thus, biomedical sciences are looking forward for a cheaper, faster, precise and accurate analytical methodology to quantify these compounds in a suitable format for the clinical environment. Therefore the objective of this study was the development of a simple, inexpensive and appropriate methodology to use at the clinical level. To achieve this goal, a procedure integrating a digitally controlled (eVol®) microextraction by packed sorbent (MEPS) and an ultra performance liquid chromatography (UPLC) coupled to a photodiode array detector (PDA) was developed to identify and quantify Hcys vitamins B6, B9 and B12. Although different conditions were assayed, we were not able to combine Hcys with the vitamins in the same analytical procedure, and so we proceeded to the optimization of two methods differing only in the composition of the gradient of the mobile phase and the injected volume. It was found that MEPS did not bring any benefit to the quantification of the Hcys in the plasma. Therefore, we developed and validate an alternative method that uses the direct injection of treated plasma (reduced and precipitated). This same method was evaluated in terms of selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), matrix effect and precision (intra-and inter-day) and applied to the determination of Hcys in a group composed by patients presenting augmented CVD risk. Good results in terms of selectivity and linearity (R2> 0.9968) were obtained, being the values of LOD and LOQ 0.007 and 0.21 mol / L, respectively. The intra-day precision (1.23-3.32%), inter-day precision (5.43-6.99%) and the recovery rate (82.5 to 93.1%) of this method were satisfactory. The matrix effect (>120%) was, however, higher than we were waiting for. Using this methodology it was possible to determine the amount of Hcys in real plasma samples from individuals presenting augmented CVD risk. Regarding the methodology developed for vitamins, despite the optimization of the extraction technique and the chromatographic conditions, it was found that the levels usually present in plasma are far below the sensitivity we obtained. Therefore, further optimizations of the methodology developed are needed. As conclusion, part of the objectives of this study was achieved with the development of a quick, simple and cheaper method for the quantification of Hcys.

Homocysteine and cardiovascular disease in renal disease

Elevated homocysteine (hyperhomocysteinaemia) in renal patients is a major concern for physicians. Although cause and effect between homocysteine and cardiovascular disease (CVD) has not been established in either the general population or renal patients, there is much evidence that this relationship does exist. Purported mechanisms that may explain this effect include increases in endothelial injury, smooth muscle cell proliferation, low-density lipoprotein oxidation and changes in haemostatic balance. Renal patients have a much greater incidence of hyperhomocysteinaemia and this may be explained by decreases in either the renal or extrarenal metabolism of the compound. We conclude that data from long-term placebo-controlled trials are urgently required to determine whether hyperhomocysteinaemia in renal patients is a cause of CVD events and requires therapeutic targeting.

Secondary prevention of renal and cardiovascular disease: Results of a renal and cardiovascular treatment program in an Australian aboriginal community

Australian Aborigines are experiencing an epidemic of renal and cardiovascular disease. In late 1995 we introduced a treatment program into the Tiwi community, which has a three- to fivefold increase in death rates and a recent annual incidence of treated ESRD of 2760 per million. Eligible for treatment were people with hypertension, diabetics with micro or overt albuminuria, and all people with overt albuminuria. Treatment centered around use of perindopril (Coversyl, Servier), with other agents added to reach BP goals; attempts to control glucose and lipid levels; and health education. Thirty percent of the adult population, or 267 people, were enrolled, with a mean follow up of 3.39 yr. Clinical parameters were followed every 6 mo, and rates of terminal endpoints were compared with those of 327 historical controls matched for baseline disease severity, followed in the pretreatment program era. There was a dramatic reduction in BP in the treatment group, which was sustained through 3 yr of treatment. Albuminuria and GFR stabilized or improved. Rates of natural deaths were reduced by an estimated 50% (P = 0.012); renal deaths were reduced by 57% (P = 0.038); and nonrenal deaths by 46% (P = 0.085). Survival benefit was suggested at all levels of overt albuminuria, and regardless of diabetes status, baseline BP, or prior administration of angiotensin converting enzyme inhibitors (ACEI). No significant benefit was apparent among people without overt albuminuria, nor among those with GFR less than 60 ml/min. An estimated 13 renal deaths and 10 nonrenal deaths were prevented, with the number-needed-to-treat to avoid one terminal event of only 11.6. Falling deaths and renal failure in the whole community support these estimates. The program was extremely cost-effective. Programs like this should be introduced to all high-risk communities as a matter of urgency.

Skeletal muscle and nuclear hormone receptors: Implications for cardiovascular and metabolic disease

Skeletal muscle is a major mass peripheral tissue that accounts for similar to 40% of the total body mass and a major player in energy balance. It accounts for > 30% of energy expenditure, is the primary tissue of insulin stimulated glucose uptake, disposal, and storage. Furthermore, it influences metabolism via modulation of circulating and stored lipid (and cholesterol) flux. Lipid catabolism supplies up to 70% of the energy requirements for resting muscle. However, initial aerobic exercise utilizes stored muscle glycogen but as exercise continues, glucose and stored muscle triglycerides become important energy substrates. Endurance exercise increasingly depends on fatty acid oxidation (and lipid mobilization from other tissues). This underscores the importance of lipid and glucose utilization as an energy source in muscle. Consequently skeletal muscle has a significant role in insulin sensitivity, the blood lipid profile, and obesity. Moreover, caloric excess, obesity and physical inactivity lead to skeletal muscle insulin resistance, a risk factor for the development of type II diabetes. In this context skeletal muscle is an important therapeutic target in the battle against cardiovascular disease, the worlds most serious public health threat. Major risk factors for cardiovascular disease include dyslipidemia, hypertension, obesity, sedentary lifestyle, and diabetes. These risk factors are directly influenced by diet, metabolism and physical activity. Metabolism is largely regulated by nuclear hormone receptors which function as hormone regulated transcription factors that bind DNA and mediate the pathophysiological regulation of gene expression. Metabolism and activity, which directly influence cardiovascular disease risk factors, are primarily driven by skeletal muscle. Recently, many nuclear receptors expressed in skeletal muscle have been shown to improve glucose tolerance, insulin resistance, and dyslipidernia. Skeletal muscle and nuclear receptors are rapidly emerging as critical targets in the battle against cardiovascular disease risk factors. Understanding the function of nuclear receptors in skeletal muscle has enormous pharmacological utility for the treatment of cardiovascular disease. This review focuses on the molecular regulation of metabolism by nuclear receptors in skeletal muscle in the context of dyslipidemia and cardiovascular disease. (c) 2005 Published by Elsevier Ltd.

Adult obesity and number of years lived with and without cardiovascular disease

Objective: To determine the differences in number of years lived free of cardiovascular disease (CVD) and number of years lived with CVD between men and women who were obese, pre-obese, or normal weight at 45 years of age. Research Methods and Procedures: We constructed multistate life tables for CVD, myocardial infarction, and stroke, using data from 2551 enrollees (1130 men) in the Framingham Heart Study who were 45 years of age. Results: Obesity and pre-obesity were associated with fewer number of years free of CVD, myocardial infarction, and stroke and an increase in the number of years lived with these diseases. Forty-five-year-old obese men with no CVD survived 6.0 years [95% confidence interval (CI), 4.1; 8.1] fewer than their normal weight counterparts, whereas, for women, the difference between obese and normal weight subjects was 8.4 years (95% CI: 6.2; 10.8). Obese men and women lived with CVD 2.7 (95% CI: 1.0; 4.4) and 1.4 years (95% CI: -0.3; 3.2) longer, respectively, than normal weight individuals. Discussion: In addition to reducing life expectancy, obesity before middle age is associated with a reduction in the number of years lived free of CVD and an increase in the number of years lived with CVD. Such information is paramount for preventive and therapeutic decision-making by individuals and practitioners alike.

Physical activity for people with cardiovascular disease: recommendations of the National Heart Foundation of Australia

* To provide physical activity recommendations for people with cardiovascular disease, an Expert Working Group of the National Heart Foundation of Australia in late 2004 reviewed the evidence since the US Surgeon General’s Report: physical activity and health in 1996. * The Expert Working Group recommends that: o people with established clinically stable cardiovascular disease should aim, over time, to achieve 30 minutes or more of moderate intensity physical activity on most, if not all, days of the week; o less intense and even shorter bouts of activity with more rest periods may suffice for those with advanced cardiovascular disease; and o regular low-to-moderate level resistance activity, initially under the supervision of an exercise professional, is encouraged. * Benefits from regular moderate physical activity for people with cardiovascular disease include augmented physiological functioning, lessening of cardiovascular symptoms, enhanced quality of life, improved coronary risk profile, superior muscle fitness and, for survivors of acute myocardial infarction, lower mortality. * The greatest potential for benefit is in those people who were least active before beginning regular physical activity, and this benefit may be achieved even at relatively low levels of physical activity. * Medical practitioners should routinely provide brief, appropriate advice on physical activity to people with well-compensated, clinically stable cardiovascular disease.

Volumetric and areal bone mineral density measures are associated with cardiovascular disease in older men and women: The health, aging, and body composition study

The associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with prevalent cardiovascular disease (CVD) and subclinical peripheral arterial disease (PAD) were investigated in a cohort of older men and women enrolled in the Health, Aging, and Body Composition Study. Participants were 3,075 well-functioning white and black men and women (42% black, 51% women), aged 68-80 years. Total hip, femoral neck, and trochanter aBMD were measured using dual-energy X-ray absorptiometry. Quantitative computed tomography was used to evaluate spine trabecular, integral, and cortical vBMD measures in a subgroup (n = 1,489). Logistic regression was performed to examine associations of BMD measures with CVD and PAD. The prevalence of CVD (defined by coronary heart disease, PAD, cerebrovascular disease, or congestive heart failure) was 29.8%. Among participants without CVD, 10% had subclinical PAD (defined as ankle-arm index < 0.9). Spine vBMD measures were inversely associated with CVD in men (odds ratio of integral [ORintegral] = 1.34, 95% confidence interval [CI] 1.10-1.63; ORtrabecular = 1.25, 95% CI 1.02-1.53; ORcortical = 1.36, 95% CI 1.11-1.65). In women, for each standard deviation decrease in integral vBMD, cortical vBMD, or trochanter aBMD, the odds of CVD were significantly increased by 28%, 27%, and 22%, respectively. Total hip aBMD was associated with subclinical PAD in men (OR = 1.39, 95% CI 1.03-1.84) but not in women. All associations were independent of age and shared risk factors between BMD and CVD and were not influenced by inflammatory cytokines (interleukin-6 and tumor necrosis factors-alpha). In conclusion, our results provide further evidence for an inverse association between BMD and CVD in men and women. Future research should investigate common pathophysiological links for osteoporosis and CVD.

Rheumatoid arthritis: links with cardiovascular disease and the receptor for advanced glycation end products

Cardiovascular (CV) disease is increased in patients with chronic inflammatory disease, including rheumatoid arthritis (RA). Furthermore it has become clear at a pathophysiological level, that atherosclerosis has striking similarities with autoimmune disease. This realization has come at a time of paradigm shift in how rheumatologists manage RA, with the availability of biological agents targeting key inflammatory cytokines. This review will focus on the possible causes of increased vascular disease in RA, including the role of traditional CV risk factors. Mechanisms potentially at play, such as C-reactive protein (CRP), altered coagulation, and cyclooxygenase (COX) -2 inhibitors will be covered in brief. The Receptor for Advanced Glycation End Products (RAGE) has been identified as a candidate molecule influencing response to ongoing inflammation and autoimmunity. There will be a focus on the role of RAGE in CV disease and RA. As has been the case with many novel molecules, functional polymorphisms are thought to alter disease expression and assist us in coming to terms with the biological activities of the parent molecule. The review will conclude with a discussion of the potential role of the RAGE Glycine 82 Serine polymorphism

Intermittent fasting:a dietary intervention for prevention of diabetes and cardiovascular disease?

Intermittent fasting, in which individuals fast on consecutive or alternate days, has been reported to facilitate weight loss and improve cardiovascular risk. This review evaluates the various approaches to intermittent fasting and examines the advantages and limitations for use of this approach in the treatment of obesity and type 2 diabetes. © The Author(s) 2013.

An examination of the UK community pharmacist's role in facilitating patient self-management of cardiovascular disease through lifestyle behaviours

The progression of cardiovascular disease (CVD) is largely modifiable through lifestyle behaviours. UK pharmacists are contractually obliged to facilitate patient self-management of chronic conditions such as CVD. Pharmacists are easily accessible health professionals who are well placed to identify “at risk” patients through medication regimes. Research has identified varying attitudes towards and levels of involvement in pharmacist-led health promotion activity. Given the diverse and exploratory nature of the work, a pragmatic, mixed methods approach was used to explore community pharmacists’ role in facilitating patient self-management of CVD. The thesis presents four studies: a qualitative study with pharmacists; a cross sectional questionnaire of community pharmacists; a systematic review and a qualitative study with patients with CVD. The qualitative study with pharmacists gave an insight into pharmacists’ experiences of giving patients with CVD lifestyle advice and the factors underpinning commonly cited barriers to providing public health services. This informed the development of the cross-sectional questionnaire which identified the predictors of pharmacists’ intentions to give two different types of advice to facilitate patient self-management. The systematic review identified a small number of interventions to prepare pharmacists to facilitate patient lifestyle behaviour change and evaluated the theories and behaviour change techniques used in successful interventions; however due to poor study quality and poor reporting of the interventions limited conclusions about the efficacy of the interventions could reliably be drawn. Finally, the qualitative study gave an insight into the experiences of patients with CVD using community pharmacy services and their expectations of the service they receive from community pharmacists. Recommendations about changes to pharmacy policy and practice in order to support pharmacists’ provision of CVD self-management advice are made.

Patients’ perceptions and experiences of cardiovascular disease and diabetes prevention programmes:a systematic review and framework synthesis using the Theoretical Domains Framework

Background - This review provides a worked example of ‘best fit’ framework synthesis using the Theoretical Domains Framework (TDF) of health psychology theories as an a priori framework in the synthesis of qualitative evidence. Framework synthesis works best with ‘policy urgent’ questions. Objective - The review question selected was: what are patients’ experiences of prevention programmes for cardiovascular disease (CVD) and diabetes? The significance of these conditions is clear: CVD claims more deaths worldwide than any other; diabetes is a risk factor for CVD and leading cause of death. Method - A systematic review and framework synthesis were conducted. This novel method for synthesizing qualitative evidence aims to make health psychology theory accessible to implementation science and advance the application of qualitative research findings in evidence-based healthcare. Results - Findings from 14 original studies were coded deductively into the TDF and subsequently an inductive thematic analysis was conducted. Synthesized findings produced six themes relating to: knowledge, beliefs, cues to (in)action, social influences, role and identity, and context. A conceptual model was generated illustrating combinations of factors that produce cues to (in)action. This model demonstrated interrelationships between individual (beliefs and knowledge) and societal (social influences, role and identity, context) factors. Conclusion - Several intervention points were highlighted where factors could be manipulated to produce favourable cues to action. However, a lack of transparency of behavioural components of published interventions needs to be corrected and further evaluations of acceptability in relation to patient experience are required. Further work is needed to test the comprehensiveness of the TDF as an a priori framework for ‘policy urgent’ questions using ‘best fit’ framework synthesis.

Coronary heart disease risk factors among tri-ethnic students at Florida International University

The present study identified and compared Coronary Heart Disease (CHD) risk factors quantified as “CHD risk point standards” (CHDRPS) among tri-ethnic (White non-Hispanic [WNH], Hispanic [H], and Black non-Hispanic [BNH]) college students. All 300 tri-ethnic subjects completed the Cardiovascular Risk Assessment Instruments and had blood pressure readings recorded on three occasions. The Bioelectrical Impedance Analysis (BIA) was used to measure body composition. Students' knowledge of CHD risk factors was also measured. In addition, a 15 ml fasting blood sample was collected from 180 subjects and blood lipids and Homocysteine (tHcy) levels were measured. Data were analyzed by gender and ethnicity using one-way Analysis of Variance (ANOVA) with Bonferroni's pairwise mean comparison procedure, Pearson correlation, and Chi-square test with follow-up Bonferroni's Chi-square tests. ^ The mean score of CHDRPS for all subjects was 19.15 ± 6.79. Assigned to the CHD risk category, college students were below-average risk of developing CHD. Males scored significantly (p < 0.013) higher for CHD risk than females, and BNHs scored significantly (p < 0.033) higher than WNHs. High consumption of dietary fat saturated fat and cholesterol resulted in a high CHDRPS among H males and females and WNH females. High alcohol consumption resulted in a high CHDRPS among all subjects. Mean tHcy ± SD of all subjects was 6.33 ± 3. 15 μmol/L. Males had significantly (p < 0.001) higher tHcy than females. Black non-Hispanic females and H females had significantly (p < 0.003) lower tHcy than WNH females. Positive associations were found between tHcy levels and CHDRPS among females (p < 0.001), Hs (p < 0.001), H males (p < 0.049), H females (p < 0.009), and BNH females (p < 0.005). Significant positive correlations were found between BMI levels and CHDRPS in males (p < 0.001), females (p < 0.001), WNHs (p < 0.008), Hs (p < 0.001), WNH males (p < 0.024), H males (p < 0.004) and H females (p < 0.001). The mean knowledge of CHD questions of all subjects was 71.70 ± 7.92 out of 100. The mean knowledge of CHD was significantly higher for WNH males (p < 0.039) than BNH males. A significant inverse correlation (r = 0.392, p < 0.032) was found between the CHD knowledge and CHDRPS in WNH females. The researcher's findings indicate strong gender and ethnic differences in CHD risk factors among the college-age population. ^

Beyond BMI: The “Metabolically healthy obese” phenotype & its association with clinical/subclinical cardiovascular disease and all-cause mortality -- a systematic review

Background A subgroup has emerged within the obese that do not display the typical metabolic disorders associated with obesity and are hypothesized to have lower risk of complications. The purpose of this review was to analyze the literature which has examined the burden of cardiovascular disease (CVD) and all-cause mortality in the metabolically healthy obese (MHO) population. Methods Pubmed, Cochrane Library, and Web of Science were searched from their inception until December 2012. Studies were included which clearly defined the MHO group (using either insulin sensitivity and/or components of metabolic syndrome AND obesity) and its association with either all cause mortality, CVD mortality, incident CVD, and/or subclinical CVD. Results A total of 20 studies were identified; 15 cohort and 5 cross-sectional. Eight studies used the NCEP Adult Treatment Panel III definition of metabolic syndrome to define “metabolically healthy”, while another nine used insulin resistance. Seven studies assessed all-cause mortality, seven assessed CVD mortality, and nine assessed incident CVD. MHO was found to be significantly associated with all-cause mortality in two studies (30%), CVD mortality in one study (14%), and incident CVD in three studies (33%). Of the six studies which examined subclinical disease, four (67%) showed significantly higher mean common carotid artery intima media thickness (CCA-IMT), coronary artery calcium (CAC), or other subclinical CVD markers in the MHO as compared to their MHNW counterparts. Conclusions MHO is an important, emerging phenotype with a CVD risk between healthy, normal weight and unhealthy, obese individuals. Successful work towards a universally accepted definition of MHO would improve (and simplify) future studies and aid inter-study comparisons. Usefulness of a definition inclusive of insulin sensitivity and stricter criteria for metabolic syndrome components as well as the potential addition of markers of fatty liver and inflammation should be explored. Clinicians should be hesitant to reassure patients that the metabolically benign phenotype is safe, as increased risk cardiovascular disease and death have been shown.

Socioeconomic inequalities of cardiovascular risk factors among manufacturing employees in the Republic of Ireland: a cross-sectional study

Objectives: To explore socioeconomic differences in four cardiovascular disease risk factors (overweight/obesity, smoking, hypertension, height) among manufacturing employees in the Republic of Ireland (ROI). Methods: Cross-sectional analysis of 850 manufacturing employees aged 18–64 years. Education and job position served as socioeconomic indicators. Group-specific differences in prevalence were assessed with the Chi-squared test. Multivariate regression models were explored if education and job position were independent predictors of the CVD risk factors. Cochran–Armitage test for trend was used to assess the presence of a social gradient. Results: A social gradient was found across educational levels for smoking and height. Employees with the highest education were less likely to smoke compared to the least educated employees (OR 0.2, [95% CI 0.1–0.4]; p b 0.001). Lower educational attainment was associated with a reduction in mean height. Non-linear differences were found in both educational level and job position for obesity/overweight. Managers were more than twice as likely to be overweight or obese relative to those employees in the lowest job position (OR 2.4 [95% CI 1.3–4.6]; p = 0.008). Conclusion: Socioeconomic inequalities in height, smoking and overweight/obesity were highlighted within a sub-section of the working population in ROI.